Nasal spray devices for the delivery of medicament to the nasal cavity, particularly the nasal mucosa, can be useful for the prophylaxis and/or treatment of certain diseases and disorders of the nasal cavity. Such devices are also capable of delivering medicament to the systemic circulation via the turbinates and lymphoid tissues located at the back of the nasal cavity and to the central nervous system via the olfactory region at the top of the nasal cavity.
Nasal spray devices include unit-dose (single use) devices having syringe-like mechanisms and metered-dose devices intended for multiple usage cycles. Unit dose devices are appropriate for delivering certain medicaments such as vaccines, whereas metered-dose devices are more suited to long-term dosage regimes, for example for the treatment of rhinitis. A known metered-dose device comprises a vial containing an aqueous suspension of a suitable medicament. The vial is provided with a manually operated pump adapted to atomise metered doses of the medicament formulation for delivery to the nasal cavity. Examples of this type of nasal spray device include FLIXONASE® (fluticasone propionate, GSK), NASACORT AQ® (triamcinolone acetoinide, Sanofi-Aventis) and NASONEX® (momethasone furoate monohydrate, Schering-Plough).
Although nasal spray devices having manually operated pumps have achieved some success in the marketplace, they have a number of drawbacks. For example, manually operated pumps have a relatively large actuation force which may, for some users, such as the very young and the elderly, be difficult to achieve on a repeatable basis. Moreover, variations in the applied actuation force can lead to some users receiving medicament doses with less than optimal spray characteristics.
To address the problems associated with these known metered-dose nasal spray devices, it may be contemplated to replace the manually operated pump with a pressurised aerosol canister. A typical aerosol canister comprises a cylindrical vial containing the medicament. The medicament is typically an active ingredient together with a suitable propellant. The medicament may be in the form of a solution or a suspension in the propellant and excipients may be added to facilitate dissolution of the active ingredient (e.g. co-solvents) or to stabilise the suspension (e.g. surfactants). The vial is provided with a metering valve having an axially extending valve stem. Displacement of the valve stem relative to the vial causes the dispensation of a metered dose of the medicament formulation as an aerosol. Compared to manually operated pumps, pressurised aerosol canisters require low actuation forces and provide consistent aerosol characteristics.
However, whereas pressurised metered dose inhalers (MDIs) have found broad market acceptance in devices intended for the pulmonary administration of medicaments by inhalation via the mouth into the lungs, MDIs have not found applications in nasal spray devices. It has generally been considered that nasal spray formulations cannot tolerate the excipients found in pMDI formulations. In particular, the high levels of co-solvents, such as ethanol, found in solution formulations are poorly tolerated by patients on account of the unpleasant sensation which they produce in the nasal cavity on administration. By way of an example, WO 92/06675 describes a medicament formulation for a pMDI comprising beclomethasone dipropionate, a co-solvent and an HFA propellant. The disclosure is principally directed to administration of the formulation by inhalation into the lungs via the mouth. There is a mention that the formulation may be administered nasally; however, there is no disclosure of how this method of administration can be achieved and there is no consideration of the problem of poor patient tolerability for nasal applications.